Targeted Therapies for Advanced Non-Small Cell Lung Cancer

Lung cancer is a serious health problem and the leading cause of cancer death worldwide, due to its high incidence and mortality. 85% of lung cancers are represented by the non-small cell lung cancer (NSCLC). Traditional chemotherapy has been the main treatment option in NSCLC. However, it is often associated with limited efficacy and overall poor patient survival. In recent years, molecular targeting has achieved great progress in therapeutic treatment of cancer and plays a crucial role in the current clinical treatment of NSCLC, due to enhanced efficacy on cancer tissues and reduced toxicity for normal tissues. In this review, we summarize the current targeting treatment of NSCLC, including inhibition of the epidermal growth factor receptor (EGFR), phosphatidylinositol 3-kinase (PI3Ks), mechanistic target of rapamycin (mTOR), epidermal growth factor receptor 2 (ErbB2), vascular epidermal growth factor receptor (VEGFR), kirsten human rat sarcoma protein (KRAS), mesenchymal-epithelial transition factor or hepatocyte growth factor receptor (c-MET), anaplastic lymphoma kinase (ALK), v-Raf murine sarcoma viral oncogene homolog B (BRAF). This article may serve as a guide to clinicians and researchers alike by assisting in making therapeutic decisions. Challenges of acquired drug resistance targeted therapy and imminent newer treatment modalities against NSCLC are also discussed

Nanoscale imaging of clinical specimens using pathology-optimized expansion microscopy

Expansion microscopy (ExM), a method for improving the resolution of light microscopy by physically expanding the specimen, has not been applied to clinical tissue samples. Here we report a clinically optimized form of ExM that supports nanoscale imaging of human tissue specimens that have been fixed with formalin, embedded in paraffin, stained with hematoxylin and eosin (H&E), and/or fresh frozen. The method, which we call expansion pathology (ExPath), converts clinical samples into an ExM-compatible state, then applies an ExM protocol with protein anchoring and mechanical homogenization steps optimized for clinical samples. ExPath enables ~70 nm resolution imaging of diverse biomolecules in intact tissues using conventional diffraction-limited microscopes, and standard antibody and fluorescent DNA in situ hybridization reagents. We use ExPath for optical diagnosis of kidney minimal-change disease, which previously required electron microscopy (EM), and demonstrate high-fidelity computational discrimination between early breast neoplastic lesions that to date have challenged human judgment. ExPath may enable the routine use of nanoscale imaging in pathology and clinical research